Breaking immunological toterance with a genetically encoded unnatural amino acid
AssigneeThe Scripps Research Institute
InventorsJan Grunewald, Meng-Lin Tsao, Roshan Perera, Richard A. Lerner, Vaughn V. Smider, Peter G. Schultz
Life of this patent
Estimating the term…
Abstract
The present invention comprises methods and compositions for producing and/or enhancing an immunological response in a subject against a target moiety such as a disease-related moiety by administration of an antigenic version of the target moiety having one or more unnatural amino acid and/or by administration of an antibody against a version of a target moiety having one or more unnatural amino acid which antibody is cross reactive with the natural target moiety.
Claims43
A method of producing or enhancing an immunological response in a subject against a target moiety, the method comprising:
- providing an unnatural immunogen, which unnatural immunogen comprises one or more unnatural amino acids;
- and,
- administering the unnatural immunogen to the subject, wherein the subject produces one or more antibodies against the unnatural immunogen, which antibodies are cross-reactive against the target moiety;
- thereby producing or enhancing the immunological response against the target moiety.
(canceled)
(canceled)
(canceled)
16-17. (canceled)
(canceled)
26-27. (canceled)
A method of prophylactically or therapeutically treating a disease state in a subject, the method comprising:
- administering an unnatural immunogen to the subject, which immunogen comprises one or more unnatural amino acids and which unnatural immunogen stimulates production of antibodies within the subject that are cross-reactive against one or more target moieties in the subject, or against one or more target moieties capable of being within the subject, that are associated with the disease state.
A method of prophylactically or therapeutically treating a disease state in a subject, the method comprising:
- producing an antibody against one or more target moieties, such producing comprising making an antibody against an unnatural immunogen which unnatural immunogen comprises one or more unnatural amino acids, and which antibody is cross-reactive against the target moiety;
- and,
- administering the antibody to the subject.
36-70. (canceled)
A method of producing a vaccine, the method comprising:
- identifying a target moiety for antibody therapy, which target moiety does not comprise an unnatural amino acid;
- providing an unnatural immunogen, which unnatural immunogen comprises one or more unnatural amino acids, and which unnatural immunogen is structurally similar to the target moiety such that when administered to a subject, the subject will produce antibodies against the unnatural immunogen that are cross-reactive against the target moiety;
- and,
- admixing the unnatural immunogen with one or more pharmaceutically acceptable adjuvant, carrier or excipient, thus producing the vaccine.
72-103. (canceled)
A method of producing an unnatural TNFα in a cell, which unnatural TNFα comprises pNO2Phe86-TNFα, the method comprising:
- growing the cell in an appropriate medium, wherein the cell comprises a nucleic acid that comprises at least one selector codon at amino acid position 86 and which nucleic acid encodes a TNFα;
- and,
- providing the pNO2Phe;
- wherein the cell further comprises:
- an orthogonal-tRNA (O-tRNA) that recognizes the selector codon;
- and,
- an orthogonal aminoacyl-tRNA synthetase (O—RS) that preferentially animoacylates the O-tRNA with the pNO2Phe and incorporates the pNO2Phe into amino acid position 86 in response to the selector codon, thereby producing the unnatural TNFα.
An unnatural TNFα, which TNFα comprises pNO2Phe86-mTNFα.
An unnatural TNFα, which TNFα comprises a TNFα selected from the group consisting of:
- a pNO2Phe11-mTNFα, a pNO2Phe19-mTNFα, a pNO2Phe21-mTNFα, a pNO2Phe42-mTNFα, a pNO2Phe49-mTNFα, a pNO2Phe11-mTNFα, and a pNO2Phe113-mTNFα.
An unnatural TNFα, which TNFα comprises a TNFα selected from the group consisting of:
- a pNO2Phe11-hTNFα, a pNO2Phe19-hTNFα, a pNO2Phe21-hTNFα, a pNO2Phe42-hTNFα, a pNO2Phe49-hTNFα, a pNO2Phe87-hTNFα, a pNO2Phe105-hTNFα, and a pNO2Phe114-hTNFα.
108-111. (canceled)
An unnatural RBP4, which RBP4 comprises a pNO2Phe43 mRBP4.
113-120. (canceled)
Dependencies are inferred from the claim text.